A Lewis Lung carcinoma line resistant to PALA (NSC-224131) was developed as a tool to elucidate the biochemical basis for the unique spectrum of antitumor activity exhibited by this agent. In a continuing study, additional experiments were performed to determine the mechanism of cytotoxicity of AMSA (NSC-141549) and to determine the basis for its in vivo selective toxicity. Rat liver glutathione-S-transferases were purified to homogeneity and the properties of these enzymes from developing mouse tissues studied as a basis for understanding the selective toxicity exhibited by certain antitumor agents. A limited study was performed on the interaction of two new anthracenedione derivatives (NSC-279836 and NSC-287513) with DNA and the resultant effect on the template activity of DNA as determined by inhibition of DNA-dependent RNA polymerase. Several new 5'-methylphosphonate analogues of anti-tumor pyrimidine mononucleotides are being synthesized based on the results from a biologic study of ara-C-5'-methylphosphonate.